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@#AIM: To observe the effect of AGGF1 on the proliferation, migration and tube formation of retinal endothelial cells in diabetic retinal tissue and high glucose conditions.<p>METHODS: C57BL/6J mice were randomly divided into the control group and diabetic retinopathy(DR)model group. The cultured rhesus monkey choroido-retinal endothelial cells(RF/6A cells)were randomly divided into the control group(cultured in low-glucose environment)and the high-glucose group(cultured in medium with 25mmol/L D-glucose), and the AGGF1 protein expression in the cells was detected by immunofluorescence assay. RF/6A cells were then divided into the control group and AGGF1 treatment group, and cell proliferation, migration and tube formation was detected by CCK-8, Transwell and Matrigel, respectively.<p>RESULTS: AGGF1 protein was expressed in all layers of the retinas and in vascular endothelial cells. The expression of AGGF1 in the retinas of DR group(0.17±0.05)was significantly higher than that of the control group(0.07±0.02)(<i>P</i><0.05). AGGF1 protein was expressed in RF/6A cells in both the high glucose group and the control group, and the expression of AGGF1 in RF/6A cells under high glucose was significantly higher(0.63±0.10)than that in the control group(0.40±0.03)(<i>P</i><0.05). After 12h of treatment, the cell proliferation rate(114.88%±0.84%)in the AGGF1 group was significantly higher than that in the control group(100.00%±2.17%)(<i>P</i><0.05). After 24h of treatment, the cell proliferation rate of the AGGF1 group(157.35%±1.89%)was significantly higher than that of the control group(142.77%±0.50%)(<i>P</i><0.05). After 48h of treatment, the cell proliferation rate of the AGGF1 group(185.39%±1.90%)was significantly higher than that of the control group(160.17%±1.33%)(<i>P</i><0.05). After 12h of treatment, the number of migrated cells(127.00±7.00)in the AGGF1 group was significantly higher than that in the control group(90.33±6.66)(<i>P</i><0.05). After 12h of treatment, the number of tube formation(33.67±1.15)in the AGGF1 group was significantly higher than that in the control group(15.33±3.51)(<i>P</i><0.05). The total tube length in AGGF1 group(8226.33±288.55)μm was significantly higher than that in the control group(6463.33±938.01)μm(<i>P</i><0.05).<p>CONCLUSION: The expression of AGGF1 protein was significantly increased in diabetic retinal tissues and retinal vascular endothelial cells induced by high glucose. AGGF1 can promote the proliferation, migration and tube formation of retinal vascular endothelial cells, suggesting that AGGF1 may be involved in retinal neovascularization of DR.
ABSTRACT
Angiogenic factor with G and FHA domain 1 (AGGF1) is an identified angiogenic factor in recent years,which is highly expressed in vascular endothelial cells and exhibits the same function as vascular endothelial growth factor,and can promote angiogenesis.Recently,it has been found that AGGF1 is highly expressed in various tumors such as liver cancer,leukemia,glioma and gastric cancer.Based on its participation in the regulation of tumor angiogenesis,DNA repair and autophagy,tumors with high expression of AGGF1 are prone to drug resistance and metastasis,and the survival and prognosis of patients are worse.Deep understanding of the roles of AGGF1 in tumor angiogenesis and its specific molecular mechanisms will provide new strategies for anti-tumor angiogenesis therapy in the future.
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Background:Angiogenesis plays a critical role in tumor growth and metastasis. AGGF1,a new member of angiogenic factors,has been shown to be aberrantly expressed in a variety of malignant tumors. Aims:To investigate the correlation of AGGF1 expression with prognosis of patients with colon cancer. Methods:Eighty colon cancer patients undergoing surgical operation from Jan. 2010 to Dec. 2012 at Xi’an First Hospital were recruited. Immunohistochemistry was performed to evaluate the expression of AGGF1 in cancerous and paired paracancerous tissues. The correlations of AGGF1 expression in cancerous tissue with clinicopathological characteristics and prognosis were analyzed. Cox regression model was used to identify the prognostic factors of colon cancer. Results:AGGF1 expression was significantly higher in colon cancer tissue than in paracancerous tissue (67. 5% vs. 32. 5%,P＜0. 05),and was correlated with tumor differentiation,lymph node metastasis,vascular/lymphatic infiltration and TNM stage (P＜0. 05). Kaplan-Meier survival analysis showed that high AGGF1 expression was correlated with decrease of survival rate in colon cancer patients (P ＜0. 05). Univariate and multivariate analyses identified AGGF1 as a prognostic factor of patients with colon cancer (OR＝2. 09,95% CI:1. 67-4. 45,P＝0. 011;OR ＝1. 98,95% CI:1. 72-4. 59,P ＝0. 000 ). Conclusions:Angiogenic factor AGGF1 is up-regulated and correlated with tumor metastasis and unfavorable prognosis in patients with colon cancer. It might be a potential prognostic indicator and deserves further study.
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Objective To investigate the expressions of AGGF1 in esophageal squamous cell carcinoma (ESCC) and their relationships with clinical features and prognosis of ESCC. Methods The expressions of AGGF1 in 70 cases of ESCC and 30 cases of normal esophageal tissue were examined using SP immunohistochemical staining and were analyzed according to the clinical features and follow-up data. Results The expressions of AGGF1 in 70 cases of ESCC was significantly higher than those in 30 cases of normal esophageal tissue [54.29%(38/70) vs. 23.33%(7/30)](P=0.004). The expressions of AGGF1 in ESCC were significantly related to the TNM stage, clinical stage and prognosis (P all<0.05). The OS was shorter in the positive teams of AGGF1 than that in the negative teams [(19.7 ± 3.5) months vs. (33.2 ± 4.0) months] (P=0.015). Cox- proportional multivariate analysis showed that positive expressions of AGGF1 and VEGF (P=0.043, 0.024) and clinical stage (P=0.035) were significant prognostic factors in overall survival. Conclusions AGGF1 has high expressions in ESCC, and it is closely related to the clinical features and prognosis of ESCC.